Lecture 7: Introduction to Selection September 11, 2015

Last Time Effects of inbreeding on heterozygosity and genetic diversity Estimating inbreeding coefficients from pedigrees Mixed mating systems Inbreeding equilibrium

Today Inbreeding and selection: inbreeding depression The basic selection model Dominance and selection

Relatedness in Natural Populations White-toothed shrew inbreeding (Crocidura russula) (Duarte et al. 2003, Evol. 57:638-645) Breeding pairs defend territory Some female offspring disperse away from parents How much inbreeding occurs? 12 microsatellite loci used to calculate relatedness in population and determine parentage 17% of matings from inbreeding Number of matings Relatedness Parental Relatedness Offspring Heterozygosity

What will be the long-term effects of inbreeding on this shrew population?

Inbreeding and allele frequency Inbreeding alone does not alter allele frequencies Yet in real populations, frequencies DO change when inbreeding occurs What causes allele frequency change? Why do so many adaptations exist to avoid inbreeding?

Natural Selection Non-random and differential reproduction of genotypes Preserve favorable variants Exclude nonfavorable variants Primary driving force behind adaptive evolution of quantitative traits

Fitness Very specific meaning in evolutionary biology: Relative competitive ability of a given genotype Usually quantified as the average number of surviving progeny of one genotype compared to a competing genotype, or the relative contribution of one genotype to the next generation Heritable variation is the primary focus Extremely difficult to measure in practice. Often look at fitness components Consider only survival, assume fecundity is equal

Inbreeding, Heterozygosity, and Fitness Inbreeding reduces heterozygosity on genome-wide scale Heterozygosity of individual can be index of extent of inbreeding Multilocus Heterozygosity: Proportion of loci for which individual is heterozygous Often shows relationship with fitness Reed and Frankham 2003 Cons Biol 17:230 Correlation Between Heterozygosity and Fitness Observed Number of heterozygous loci Deng and Fu 1998 Genetics 148:1333 Simulated

Inbreeding Depression wikipedia www.myrmecos.net/ notexactlyrocketscience.wordpress.com terrierman.com/inbredthinking.htm Reduced fitness of inbred individuals compared to outcrossed individuals Negative correlation between fitness and inbreeding coefficient observed in wide variety of organisms Inbreeding depression often more prevalent under stressful conditions Lynch and Walsh 1998

Mechanisms of Inbreeding Depression Two major hypotheses: Partial Dominance and Overdominance Partial Dominance (really a misnomer) Inbreeding depression is due to exposure of recessive deleterious alleles Overdominance Inherent advantage of heterozygosity Enhanced fitness of heterozygote due to pleiotropy (one gene affects multiple traits): differentiation of allele functions Bypass homeostasis/regulation

What about long-term effects on the shrew? Fecundity (measured by number of offspring weaned) was not affected by relatedness between mating pairs or heterozygosity of individuals No evidence of inbreeding depression in this species Why not?

How do we quantify the effects of natural selection on allele frequencies over time? Can we predict and model evolution?

Relative Fitness of Diploids And NM is the best-performing genotype Consider a population of newborns with variable survival among three genotypes: A1A1 A1A2 A2A2 N 100 100 100 Survival 80 56 40 New parameter: ω, relative fitness (assuming equal fecundity of genotypes in this case) Define ω=1 for best performer; others are ratios relative to best performer: Where N11s is number of A1A1 offspring surviving after selection in current generation And NM is the best-performing genotype

Average Fitness Use genotype frequencies to calculate weighted fitness for entire population A1A1 A1A2 A2A2 ω 1 0.7 0.5 ω = D(ω11) + H(ω12) + R(ω22) ω = (100/300)(1) + (100/300)(0.7) + (100/300)(0.5) = 0.733 When fitness varies among genotypes, average fitness of the population is less than 1

Frequency After Selection D’ = D(ω11)/ω H’ = H(ω12)/ω = (0.33)(0.7)/0.733 = 0.32 R’ = R(ω22)/ω = (0.33)(0.5)/0.733 = 0.23 = (0.33)(1)/0.733 = 0.45 Selection causes increase in more fit genotype and reduction in less fit genotypes Allele Frequency Change: q = (N22 + N12/2)/N = (100 + 100/2)/300 = 0.5 q’ = (40+56/2)/176 = 0.39 Δq = q’ – q = 0.39 – 0.5 = -0.11

Over time, what will happen to p and q in this population? What is Δp in the previous example?

Starting from Allele Frequencies A1A1 A1A2 A2A2 freq0 p2 2pq q2 ω ω11 ω12 ω22 freq1 p2 ω11/ω 2pq ω12/ω q2 ω22/ω ω = p2(ω11) + 2pq(ω12) + q2(ω22) q’ = q2ω22+pqω12 ω

Change in Allele Frequencies due to Selection (i.e., evolution) q2ω22+pqω12 ω q2ω22+pqω12 - qω ω q’ - q = - q = Simplifies to: Δq =pq[q(ω22- ω12) - p(ω11 – ω12)] ω See p. 118 in your text for derivation “The single most important equation in all of population genetics and evolution!” Gillespie 2004, p. 62

Fitness effects of individual alleles Δq =pq[q(ω22 – ω12) - p(ω11- ω12)] ω Effects of substituting one allele for another Conceptually, compare fitness of homozygote to heterozygote Rate of change inversely proportional to mean fitness of population: allele frequencies don’t change much in a fit population! Marginal fitness: the effects of an individual allele on fitness (the average fitness genotypes containing that allele)

Incorporating Selection and Dominance Selection Coefficient (s) Measure of the relative fitness of one homozygote compared to another. ω11 = 1 and ω22 = 1-s s ranges 0 to 1 in most cases (more fit allele always A1 by convention) Heterozygous Effect (level of dominance) (h) Measure of the fitness of the heterozygote relative to the selective difference between homozygotes ω12 = 1 - hs

Relative Fitness (ω) ω11 ω12 ω22 Heterozygous Effect A1A1 A1A2 A2A2 Relative Fitness (ω) ω11 ω12 ω22 Relative Fitness (hs) 1 1-hs 1-s h = 0, A1 dominant, A2 recessive h = 1, A2 dominant, A1 recessive 0 < h < 1, incomplete dominance h = 0.5, additivity h < 0, overdominance h > 1, underdominance

Putting it all together A1A1 A1A2 A2A2 Relative Fitness (ω) ω11 ω12 ω22 Relative Fitness (hs) 1 1-hs 1-s Δq =pq[q(ω22 – ω12) - p(ω11- ω12)] ω Reduces to: Δq =-pqs[ph + q(1-h)] 1-2pqhs-q2s

Modes of Selection on Single Loci Directional – One homozygous genotype has the highest fitness Purifying selection AND Darwinian/positive/adaptive selection Depends on your perspective! 0 ≤ h ≤ 1 ω A1A1 A1A2 A2A2 ω A1A1 A1A2 A2A2 Overdominance – Heterozygous genotype has the highest fitness (balancing selection) h<0, 1-hs > 1 Underdominance – The heterozygous genotypes has the lowest fitness (diversifying selection) h>1, (1-hs) < (1 – s) < 1 for s > 0 ω A1A1 A1A2 A2A2

Directional Selection Δq =-pqs[ph + q(1-h)] 1-2pqhs-q2s 0 ≤ h ≤ 1 1 0.5 Δq h=0.5, s=0.1 q q Time

Relative Fitness (ω) ω11 ω12 ω22 Relative Fitness (hs) 1 1-hs 1-s Lethal Recessives A1A1 A1A2 A2A2 Relative Fitness (ω) ω11 ω12 ω22 Relative Fitness (hs) 1 1-hs 1-s For completely recessive case, h=0 What is s for lethal alleles? ω A1A1 A1A2 A2A2 0.2 0.4 0.6 0.8 1